Search Results (1,083)

Background and Objectives: Iron deficiency (ID) is common in heart failure with reduced ejection fraction (HFrEF) and is associated with adverse clinical outcomes. Although intravenous ferric carboxymaltose (FCM) improves functional status, its effects on ventricular electrophysiological indices remain incompletely characterized. This study evaluated short-term changes in the corrected index of cardiac electrophysiological balance (iCEBc) and conventional electrocardiographic repolarization parameters after FCM administration. Materials and Methods: This retrospective single-center pre–post study included 92 clinically stable patients with HFrEF and ID who received intravenous FCM. Standard 12-lead electrocardiograms and laboratory parameters were evaluated at baseline and 30 ± 5 days after treatment. The primary outcome was the within-patient change in iCEBc, while secondary outcomes included conventional ventricular repolarization indices. Results: Following FCM treatment, ferritin, transferrin saturation, and hemoglobin increased significantly (all p < 0.001). iCEBc decreased significantly (4.33 ± 1.04 vs. 4.04 ± 0.82, p = 0.016). Significant reductions were also observed in QTc, JTc, JT, Tp-e, Tp-e/QT, Tp-e/QTc, frontal QRS–T angle, and QT, whereas QRS duration remained unchanged. Changes in iron indices were not associated with changes in iCEBc. Conclusions: In this uncontrolled pre–post cohort, intravenous FCM was associated with favorable short-term changes in several electrocardiographic repolarization indices. However, because anemia correction occurred concurrently and no control group or clinical arrhythmic outcomes were available, these findings should be considered exploratory and hypothesis-generating rather than evidence of an antiarrhythmic effect. Full article

Background: In heart failure with reduced ejection fraction (HFrEF), implantable cardioverter-defibrillators (ICDs) are used for the primary prevention of sudden cardiac death, yet many patients never receive appropriate therapy, and left ventricular ejection fraction (LVEF) alone poorly discriminates who will. We investigated whether a cumulative electrical risk score (ERS) derived from the surface electrocardiogram is associated with appropriate ICD therapy. Methods: In this single-center, retrospective study, 205 patients with HFrEF who underwent ICD implantation for primary prevention were classified according to whether they had received appropriate ICD therapy. A modified eight-parameter ERS was calculated from the baseline electrocardiogram. Associations were assessed using receiver operating characteristic (ROC) analysis and logistic regression. Results: The ERS showed moderate-to-good discrimination (AUC 0.795; p < 0.001); a cut-off of 3.5 yielded 91% sensitivity and 71.4% specificity. After adjustment for age, sex, LVEF, cardiomyopathy etiology, BNP and device duration, the ERS remained independently associated with appropriate ICD therapy (adjusted OR 2.189; 95% CI 1.246–3.845; p = 0.006). Conclusions: A cumulative electrical risk score from the standard electrocardiogram was independently associated with appropriate ICD therapy and may add risk information beyond LVEF. These retrospective findings warrant prospective, multicenter validation. Full article

Background: Although delirium is an acute confusional state, the available literature identifies impaired activities of daily living (ADL) as a predisposing factor. However, the question of whether ADL is associated with delirium in older patients with heart failure (HF) has not been evaluated. This study investigated the relationship between ADL and delirium and further explored whether HF phenotype moderates the relationship in older patients with acute decompensated HF (ADHF). Methods: In older patients with ADHF, stabilized after HF admission, handgrip strength (HGS) and 6 min walk distance (6MWD) tests were performed, and ADL was assessed using the Barthel index. Delirium during hospitalization was defined according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Logistic regression analyses were used to estimate the association of physical activity and ADL with delirium during hospitalization in older patients with ADHF. Results: A total of 245 older patients (82.9 ± 6.0 years, 49.4% male) with ADHF (heart failure with preserved ejection fraction [HFpEF]; n = 107, 44%) were analyzed. In the group with delirium (n = 65, 26.5%), there was significant difference in Mini–Mental state examination (MMSE) score (19 vs. 25, p < 0.001), HGS (13 vs. 16 kg, p < 0.05), 6MWD (120 vs. 160 m, p < 0.05) and Barthel index (55 vs. 65, p < 0.05) compared to the group without delirium. In the HFpEF group, 6MWD (p < 0.05) and Barthel index (p < 0.001) had significant negative correlations with delirium. In the multiple logistic regression analysis adjusted for the confounders, Barthel index (Odds ratio: 0.390 per 1 standard deviation, p < 0.01) was significantly associated with delirium in the HFpEF group. Conclusions: In older ADHF patients, decreased physical activity and ADL were significantly correlated with delirium. Lower Barthel index was associated with delirium, and this association was significantly modified by HFpEF status. Full article

Heart failure with preserved ejection fraction (HFpEF) is a substantial global health burden and the greatest unmet medical need for cardiovascular diseases. It is marked by pronounced clinical heterogeneity and complex multi-system pathophysiology with limited therapeutic options. Progress in developing effective therapeutics is constrained by the inadequacy of experimental models to fully recapitulate the multifactorial nature of the disease. Recent evidence underscores the significant involvement of inflammatory, oxidative, and mitochondrial pathways in the pathogenesis of HFpEF, with non-coding RNAs and epigenetic regulation serving as crucial modulators and prospective therapeutic targets. This review maps the HFpEF target landscape, while critically assessing the mechanistic contributions, translational fidelity, and limitations of existing in vivo and in vitro models. Further, advances are noted among the in vitro technologies, including human cardiac organoids and engineered heart tissues integrated with high-throughput multi-omics and computational modeling, enabling in-depth examination of HFpEF mechanisms. Finally, we underscore the necessity of integrative, systems-level approaches and multi-marker strategies to enhance translational relevance, improve risk stratification, and accelerate development of mechanism-based therapies. Collectively, this review supports phenotypic-guided and mechanism-informed therapeutic development for HFpEF, and provides a roadmap for next generation model development and therapeutic innovation. Full article

Background and Clinical Significance: Heart failure with reduced ejection fraction (HFrEF) is highly prevalent among patients with end-stage kidney disease (ESKD) undergoing maintenance hemodialysis (MHD) and is associated with poor clinical outcomes. Sacubitril/valsartan (SV) is a cornerstone therapy for HFrEF; however, its use in dialysis patients remains limited due to safety concerns and lack of robust evidence. This case series describes the clinical response and safety of SV in patients with HFrEF receiving MHD; Case Presentation: Four male patients with HFrEF undergoing MHD were treated with SV and followed for 12 months. Baseline evaluation showed a left ventricular ejection fraction (LVEF) of 35.5%, left ventricular end-systolic volume (LVESV) of 118.5 mL, left ventricular end-diastolic volume (LVEDV) of 185.7 mL, pulmonary artery systolic pressure (PASP) of 52.7 mmHg, and NT-proBNP levels above 35,000 pg/mL in all patients. After 12 months of SV therapy, LVEF improved to 53.7%, corresponding to a 51.4% relative increase from baseline. Reverse cardiac remodeling was observed, with LVESV decreasing to 58.2 mL and LVEDV to 110 mL, together with reductions in left ventricular dimensions. PASP decreased to 32 mmHg, and NT-proBNP levels declined to 7261.7 pg/mL. Blood pressure improved, serum potassium remained stable at 4.95 mmol/L, and no severe hyperkalemia, intradialytic hypotension, post-dialysis hypotension, or heart failure-related hospitalization occurred; Conclusions: In this case series, SV was associated with improved cardiac function, reverse remodeling, pulmonary pressure reduction, and an acceptable safety profile in patients with HFrEF undergoing MHD. These findings suggest a potential therapeutic role for SV in selected dialysis patients and support further investigation. Full article

Background: The prognostic relevance of left ventricular ejection fraction (LVEF) categories in acute heart failure (AHF) remains debated. We compared the clinical phenotype of patients hospitalized for AHF with preserved (LVEF ≥ 50%) versus reduced (LVEF < 50%) ejection fraction (EF), and compared the prognostic influence of the two phenotypes on in-hospital and post-discharge mortality. Methods: We analyzed 530 consecutive patients enrolled in a prospective single-center AHF registry (February 2023–June 2025), followed through June 2026, grouped as preserved (LVEF ≥ 50%, n = 264) or reduced (LVEF < 50%, n = 266). Baseline characteristics, in-hospital course, and post-discharge events (death, renal replacement therapy [RRT], acute HF rehospitalization, and a triple composite) were compared. Given the distinct prognostic mechanisms operating during hospitalization and after discharge, the two periods were analyzed separately. In-hospital mortality was reported descriptively, whereas predictors of post-discharge mortality were evaluated using multivariable Cox regression with follow-up beginning at discharge. Results: Patients with preserved LVEF were older, predominantly women, and more often frail and in atrial fibrillation, whereas LVEF < 50% was associated with an ischemic etiology, right heart failure, and higher values of natriuretic peptides (all p < 0.05). In-hospital mortality was higher with LVEF < 50% (7.1% vs. 3.0%, p = 0.046) and was almost entirely cardiovascular (6.4% vs. 1.1%, p = 0.002). Among the 503 patients discharged alive, post-discharge mortality did not differ between phenotypes (27.7% vs. 22.7%, p = 0.23), nor did terminal RRT (2.7% vs. 3.2%) or the triple composite (49.6% vs. 42.1%, p = 0.11); emergency-department visits were more frequent with preserved LVEF (69.1% vs. 58.6%, p = 0.048). In the multivariable model of post-discharge mortality (n = 494, 124 deaths), frailty (HR 1.96, 95% CI 1.09–3.51) and log NT-proBNP (HR 1.86, 95% CI 1.45–2.38) were independent predictors, whereas worsening renal function was not. LVEF < 50% was associated with lower post-discharge mortality in the full model (HR 0.58, 95% CI 0.38–0.89), but this association was not robust across specifications, as follows: it disappeared when NT-proBNP was omitted (HR 0.88, 95% CI 0.60–1.27), and no alternative LVEF cut-point was associated with mortality. Conclusions: The two phenotypes are dissimilar in in-hospital mortality and similar in post-discharge mortality, with no consistent independent contribution to prognosis of this specific cut-off of LVEF of 50%. Full article

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors, originally developed as glucose-lowering agents for type 2 diabetes mellitus, have been shown in large, randomized trials to improve clinical outcomes in heart failure (HF) across the ejection fraction (EF) spectrum. The imaging-derived and hemodynamic changes that accompany these benefits remain incompletely characterized, and it is not known whether the patterns of cardiac remodeling observed differ between HF with reduced ejection fraction (HFrEF, left ventricular ejection fraction [LVEF] ≤ 40%) and HF with preserved ejection fraction (HFpEF, LVEF ≥ 50%). This systematic review synthesized randomized evidence on the effects of SGLT2 inhibitors on cardiac remodeling parameters and described the patterns observed in each phenotype. Methods: PubMed/MEDLINE, Scopus and Embase were searched for randomized controlled trials (RCTs) published between February 2016 and March 2026. Eligible studies enrolled adults with chronic HF receiving an SGLT2 inhibitor, included a non-SGLT2-inhibitor comparator and assessed cardiac structure, function or loading by echocardiography, cardiac magnetic resonance (CMR) or cardiac catheterization over at least three months. Risk of bias was assessed with Cochrane RoB 2, separately for each outcome domain and targeting the effect of assignment to intervention, and certainty of evidence with GRADE, separately by phenotype and imaging modality. A structured narrative synthesis following Synthesis Without Meta-analysis (SWiM) guidance that prioritized the direction, magnitude and precision of randomized between-group treatment effects was performed. Results: Fourteen publications from thirteen unique RCTs (1232 participants) were included: four trials enrolled HFrEF (LVEF ≤ 40%), five enrolled mixed reduced and mildly reduced EF cohorts (LVEF < 50% or 35–49%), four enrolled HFpEF (LVEF ≥ 50%) and one enrolled a mixed ejection-fraction population. No trial enrolled an exclusively HFmrEF population. In reduced EF, the direction of effect on LV volumes favored SGLT2 inhibition in four of eight trials reporting volumes, but the estimates were not compatible in magnitude, and the one adequately powered trial at low risk of bias (EFFORT) was neutral; the largest volumetric estimates came from EMPA-TROPISM, which published no adjusted between-group estimate. The only prespecified, adjusted and confidence-interval-bearing volumetric estimates were those of SUGAR-DM-HF (left ventricular end-systolic volume index −6.0 mL/m², 95% CI −10.8 to −1.2; end-diastolic volume index −8.2 mL/m², 95% CI −13.7 to −2.6). The global longitudinal strain improved in the trial with blinded core-laboratory reading (EFFORT −1.44%, 95% CI −2.42 to −0.46), but effect sizes in the open-label trials without stated reader blinding were two to three times larger, and the CMR-derived strain was unchanged. In HFpEF, volumes, EF, mass and strain were unchanged throughout. The most secure finding of the review was invasive: in CAMEO-DAPA, dapagliflozin reduced pulmonary capillary wedge pressure at rest by 3.5 mmHg (95% CI −6.6 to −0.4) and at peak exercise by 5.7 mmHg (95% CI −10.8 to −0.7). NT-proBNP results were directionally inconsistent, and the trials in which NT-proBNP was a prespecified primary endpoint (Empire HF, CANDLE) were neutral. Certainty of evidence was very low for 18 of 20 evidence profiles and low for the remaining two. Conclusions: Randomized imaging and hemodynamic studies suggest phenotype-related differences in the cardiac remodeling associated with SGLT2 inhibitor therapy. In studies enrolling patients with reduced EF, treatment was associated predominantly with reverse remodeling of left ventricular volumes and modest improvements in myocardial function, whereas in preserved EF, the observed changes were mainly confined to filling pressures and diastolic function, with no consistent evidence of left ventricular volumetric remodeling. Given the limited number of studies, substantial heterogeneity, and the overall low certainty of evidence, these findings should be considered hypothesis-generating and warrant confirmation in adequately powered phenotype-specific mechanistic trials. Full article

Pulmonary hypertension (PH) frequently complicates heart failure with reduced ejection fraction (HFrEF) and worsens prognosis. Right heart catheterization (RHC) remains the diagnostic gold standard, but natriuretic peptides may help identify patients requiring invasive assessment. We retrospectively analyzed 563 HFrEF patients who underwent RHC. Patients with and without PH were compared. Associations between B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and RHC parameters were assessed using correlations, restricted cubic splines, logistic regression and receiver operating characteristic (ROC) curves. PH was present in 443 patients (78.7%). Of the study group, 87 (15.5%) were females and 476 (84.5%) were males, the median age was 55 years and the median ejection fraction was 20%. Patients with PH had significantly higher BNP (p < 0.001), NT-proBNP (p < 0.001), New York Heart Association (NYHA) class (p < 0.001) and lower ejection fraction (p < 0.001). Increase in PH risk (p < 0.001), mean pulmonary artery pressure (p < 0.001), pulmonary vascular resistance (PVR) (p < 0.001) and pulmonary arterial wedge pressure (p < 0.001) and decrease in cardiac index (p < 0.001) were associated with an increase in BNP up to approximately 500 pg/mL and NT-proBNP up to approximately 3000 pg/mL. BNP and NT-proBNP were independent predictors of PH and PVR > 5 Wood units. BNP and NT-proBNP predicted PH with area under the curve (AUC) 0.798 and 0.727, respectively, while prediction of PVR > 5 Wood units (AUC 0.661 and 0.664, respectively) or cardiac index < 2.0 L/min/m² was less accurate (AUC 0.607 and 0.623, respectively). Measurement of plasma natriuretic peptides may support PH screening in HFrEF, but their limited ability to detect severe precapillary component confirms RHC as the definitive tool for hemodynamic phenotyping. Full article

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by typical heart failure symptoms, left ventricular ejection fraction (LVEF) ≥50%, elevated natriuretic peptides, and impaired diastolic function. HFpEF constitutes a heterogeneous clinical syndrome with increasing prevalence worldwide and limited therapeutic options. Short-chain fatty acids (SCFAs), generated by gut microbial fermentation of dietary fibers, have recently been implicated as modulators of cardiovascular physiology and pathology. In this narrative review, we synthesize evidence linking SCFAs and SCFA-related signaling to HFpEF pathophysiology, with attention to the distinction between direct HFpEF evidence and findings extrapolated from broader cardiovascular and metabolic models. Although HFpEF-specific data remain limited, available evidence suggests that SCFAs may be relevant to several disease-associated processes, including systemic inflammation, adipokine dysregulation, endothelial dysfunction, myocardial stiffness, and metabolic derangement. We further discuss receptor-mediated and histone deacetylase-dependent mechanisms, consider differences among acetate, propionate, and butyrate, and evaluate the current limitations and therapeutic implications of SCFA-related pathways in HFpEF. At present, SCFA-directed interventions should be viewed as investigational rather than established therapeutic strategies for HFpEF. Full article

Background: Transcatheter edge-to-edge repair and percutaneous mitral annuloplasty with the Carillon device are techniques used in the treatment of functional mitral regurgitation (FMR). Both approaches have been shown to have divergent clinical outcomes in patients with proportionately severe and disproportionately severe FMR. Objective: To evaluate which patients could benefit most from percutaneous mitral annuloplasty, we evaluated the possible correlation between echocardiographic parameters at baseline and their change one year after the Carillon procedure in subjects with proportionate versus disproportionate FMR. Methods: We performed a pooled analysis from three trials of patients with FMR. The main inclusion criteria included persistent grades 2+ to 4+ FMR with >5.5 cm left ventricular (LV) end-diastolic diameters (LVEDDs) and a reduced LV ejection fraction. Patients with an effective regurgitant orifice area/LV end-diastolic volume (EROA/LVEDV) ratio equal to 0.15 mm²/mL or less were assigned to the proportionate FMR group (n = 74; 65%), and those with a ratio above 0.15 mm²/mL were classified as having disproportionate FMR (n = 39; 35%). Results: In both groups, the changes in LV systolic and diastolic volumes after the procedure correlate negatively with baseline LV volumes, suggesting larger improvements (decreases) in LV volumes in patients with more pronounced LV dilatation at the baseline. In contrast to the disproportionate group, in patients with proportionate FMR, no correlation between the baseline LV diameters and improvement in LV volumes after 12 months was observed. However, higher baseline LV diameters predicted a higher degree of decrease in LV diameters in “proportionate” but not “disproportionate” FMR patients. Interestingly, the improvement in EF as a result of the Carillon implantation was not predicted by any of the baseline parameters studied. However, in both groups, the 12-month change in mitral annular area negatively correlated with baseline vena contracta but not with RV and EROA. Conclusions: In FMR patients undergoing the Carillon procedure, higher baseline LV volumes may predict more pronounced reverse remodeling, defined as a decrease in LV volumes. Higher values of vena contracta may predict larger reductions in the mitral annular area. High baseline LV diameters could suggest improvements in LV volumes in disproportionate FMR and in LV diameters in proportionate FMR, probably due to different LV geometries. Full article

Background: Pathological cardiac remodeling is a major driver of heart failure progression and is closely associated with fibroblast activation, myocardial inflammation, oxidative injury, and impaired autophagic homeostasis. Epidermal growth factor receptor (EGFR) signaling participates in adverse remodeling through activation of MAPK pathways, but the relationship between pharmacologically modulated EGFR turnover and cardiac remodeling remains insufficiently defined. Methods: This study investigated the protective effects of cycloastragenol (CAG), a triterpenoid sapogenin derived from Astragalus membranaceus, in Angiotensin II (Ang II)-induced cardiac remodeling and examined changes in EGFR turnover and associated MAPK signaling and autophagy-related processes. Circulating soluble EGFR was associated with heart failure severity after adjustment for age and sex. Separately, an independent exploratory transcriptomic analysis of left ventricular samples from GSE161472 showed that myocardial EGFR expression distinguished HFrEF from non-failing samples with an AUC of 0.870. Male C57BL/6 mice subjected to continuous Ang II infusion at 500 ng/kg/min for 28 days were used to establish the in vivo cardiac remodeling model and evaluate the effects of CAG on cardiac function, myocardial injury, fibrosis, inflammation, oxidative stress, apoptosis, and autophagy-related changes, with enalapril used as a positive control. Primary cardiac fibroblasts were further used to assess proliferation, migration, collagen production, EGFR membrane accumulation, lysosomal trafficking, MAPK signaling, and autophagic flux. Circulating soluble EGFR increased with heart failure severity and was associated with BNP elevation, ventricular dilation, and reduced ejection fraction. Results: CAG improved cardiac performance, reduced myocardial injury markers, alleviated fibrosis and hypertrophy, and suppressed inflammatory and oxidative responses in Ang II-treated mice. In cardiac fibroblasts, CAG reduced sustained EGFR membrane accumulation, increased EGFR recovery in pan-ubiquitin immunoprecipitates and lysosomal localization, and accelerated EGFR protein turnover, consistent with a predominantly lysosome-associated pathway. The K716R mutation attenuated CAG-associated changes in EGFR turnover, MAPK phosphorylation, and autophagic flux. Conclusions: These findings suggest that CAG attenuates Ang II-induced cardiac remodeling and is associated with enhanced EGFR lysosomal turnover, accompanied by changes in MAPK signaling and autophagy-related processes. Full article

Background/Objectives: Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) frequently coexist and are linked by shared risk factors and pathophysiological mechanisms. Their association is consistently related to worse clinical outcomes. This narrative review summarizes current evidence regarding the epidemiology, pathophysiology, management strategies, and prognosis of patients with AF and HFrEF. Methods: This is a narrative review based on published randomized trials, registries, and observational studies evaluating the interaction between AF and HFrEF, with a focus on therapeutic strategies including rate and rhythm control, catheter ablation, stroke prevention, and guideline-directed medical therapy. Results: AF and HFrEF have a bidirectional relationship, with each condition promoting the development and progression of the other. AF contributes to hemodynamic impairment and adverse remodeling, while HFrEF promotes atrial structural and electrical changes. Management remains complex. Rate control is commonly achieved with beta-blockers and digoxin, while rhythm control is limited by the safety profile of antiarrhythmic drugs. Catheter ablation has shown improvements in left ventricular function and, in selected patients, reductions in hospitalizations and mortality, although results are not consistent across all trials. Guideline-directed medical therapy improves outcomes in HFrEF, but its interaction with AF varies across drug classes. Stroke risk is significantly increased, requiring appropriate anticoagulation. Patients with AF and HFrEF have an increased risk of mortality, hospitalization, and adverse clinical events compared with those with either condition alone, although the extent to which these outcomes are attributable to AF itself, HF severity, or the associated comorbidity burden remains uncertain. Conclusions: The coexistence of AF and HFrEF identifies a high-risk population with complex management and unfavorable outcomes. While advances in rhythm control and heart failure therapies have improved selected outcomes, optimal treatment strategies and their impact on long-term prognosis remain incompletely defined. Full article

Cardiac rehabilitation (CR) is a multicomponent secondary prevention intervention that improves functional capacity and quality of life across cardiac diagnoses, yet remains markedly underused in heart failure (HF). Existing reviews treat efficacy, coverage, delivery, and equity separately; this narrative review integrates them to clarify why uptake in HF remains low despite an established evidence base. We searched PubMed/MEDLINE and the Cochrane Library from January 2009 through December 2025, prioritizing clinical practice guidelines, landmark trials, systematic reviews, registry analyses, and U.S. policy documents, with narrative synthesis across efficacy, coverage, delivery, and equity. In heart failure with reduced ejection fraction (HFrEF), exercise-based CR consistently improves peak oxygen consumption by roughly 15 to 17 percent, improves health status, and reduces short-term all-cause hospitalization. In heart failure with preserved ejection fraction (HFpEF), supervised exercise improves functional capacity and quality of life, but a large pragmatic outcome trial and Medicare coverage remain lacking. In appropriately selected, clinically stable patients, hybrid and virtual delivery produce comparable short-term functional and quality-of-life gains, with more limited direct evidence for hard clinical endpoints. Closing the HFpEF coverage gap, automating HFrEF referral, diversifying delivery, and embedding equity across the CR pipeline are actionable priorities for realizing CR’s potential in HF. Full article

Chronic heart failure (CHF) is a growing global health concern characterized, in part, by progressive sympathetic overactivation, which exacerbates this condition. Accumulating evidence identifies oxidative stress as a key driver of sympatho-excitation, mediated by excess reactive oxygen species (ROS) and impaired antioxidant defenses. The redox-sensitive transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) is a central regulator of antioxidant gene expression, but its role in the peripheral sympathetic nervous system, particularly in the stellate ganglia, remains unclear. We hypothesized that Nrf2 signaling is disrupted in the stellate ganglia in CHF and that modulation of Nrf2 alters ROS levels and sympathetic responses. In rats, six weeks post myocardial infarction (MI), the stellate ganglia exhibited increased ROS levels in tyrosine hydroxylase-positive neurons along with reduced Nrf2 protein and mRNA expression; both changes were inversely associated with ejection fraction (EF). To determine the functional role of Nrf2, lentiviral vectors encoding GFP or GFP-Nrf2 were delivered to the stellate ganglia three weeks after MI. Nrf2 upregulation attenuated heart rate responses to stellate stimulation in sham rats but augmented responses in CHF rats. The increase in plasma norepinephrine levels was reduced following stellate stimulation in CHF rats that overexpressed Nrf2, while β1-adrenergic responsiveness to dobutamine was unchanged. This study demonstrates that CHF is associated with increased oxidative stress and reduced Nrf2 expression in the stellate ganglion. Nrf2 overexpression significantly modulated sympathetic regulation, altering heart rate responses and reducing plasma norepinephrine in CHF rats. These findings support the concept that impaired Nrf2 signaling contributes to ganglionic redox imbalance and dysregulated sympathetic nerve activity in CHF. Full article

Atrial fibrillation (AF) and heart failure (HF) frequently coexist, but the clinical relevance of AF may differ according to whether it appears to be a potentially reversible contributor, an aggravating factor in established HF, or a marker of advanced substrate. The driver–modifier–marker lens used in this review is a provisional, nonvalidated aid to clinical reasoning and should not be interpreted as a treatment score. This narrative review was informed by dated searches of PubMed/MEDLINE, the Cochrane Library, and OpenAlex through 29 July 2026, followed by a targeted update on 30 July 2026. It considers HF with reduced, mildly reduced, and preserved ejection fraction together with AF timing, burden, ventricular-rate exposure, myocardial substrate, and reversibility. Early rhythm control may be particularly relevant when AF is recent or temporally associated with ventricular dysfunction, symptoms, decompensation, or inadequate cardiac resynchronization therapy delivery. Evidence supporting catheter ablation is most direct in suspected AF-mediated cardiomyopathy and selected HFrEF populations, whereas evidence in HFpEF more consistently supports symptom relief, improved exercise hemodynamics, and AF-burden reduction than mortality reduction. Pulmonary vein isolation remains the procedural foundation. Radiofrequency, cryoballoon, and pulsed-field ablation are effective in broad AF populations, but HF phenotype-specific prognostic superiority has not been established for any energy source. Clinical decisions should reflect the design and directness of the evidence together with expected benefit, rhythm durability, procedural risk, patient-reported outcomes, stroke prevention, guideline-directed HF therapy, risk-factor management, and patient preference. Full article